Systems for treating dermal inflammatory conditions

ABSTRACT

The present invention is directed to novel systems and methods for treating dermal inflammatory disorders, such as psoriasis.

CROSS-REFERENCE

This application is a continuation of U.S. application Ser. No.15/625,781, filed Jun. 16, 2017, which claims the benefit of U.S.provisional application Nos. 62/351,429 filed Jun. 17, 2016, and62/436,548, filed Dec. 20, 2016, which applications are incorporatedherein by reference.

STATEMENT REGARDING FEDERALLY FUNDED RESEARCH

None.

REFERENCE TO SEQUENCE LISTING

None.

BACKGROUND Field of the Invention

The present invention relates generally to the fields of compositionsand methods for treating dermal inflammatory conditions, such as, butnot limited to psoriasis.

Dermal inflammatory conditions are prevalent and cause considerablediscomfort and can have significant psycho-social impact for numerouspatients. While some treatments include expensive medications requiringprescriptions, many of these can cause long term topical or systemicside effects that limit their use, or they are ineffective and tooexpensive for many patients in need.

SUMMARY

In one embodiment, principles of the present disclosure provide a systemfor treating dermal inflammation said system comprising ananti-microbial gel, a treatment gel comprising curcumin and amoisturizer comprising bromelain. In some embodiments, each of saidanti-microbial gel, treatment gel and moisturizer are in separatecontainers. In some embodiments the treatment gel comprises curcumin,bromelain and a pharmaceutically acceptable carrier for topicalapplication. In some embodiments the system further comprises ananhydrous formulation of salicylic acid.

In one embodiment principles of the present disclosure provide a methodof treating psoriasis comprising applying a composition of the systemdescribed above, comprising an anti-microbial gel comprising at leastsodium chlorite, a treatment gel comprising at least turmeric orcurcumin, and a moisturizer comprising at least bromelain to the skin ofa patient in need thereof. In some embodiments the antimicrobial gelcomprises sodium chlorite and optionally may contain benzalkoniumchloride. In some embodiments the treatment gel contains salicylic acidand curcumin. In some embodiments coal tar is contained in the treatmentgel.

It is contemplated that any embodiment of a method or compositiondescribed herein can be implemented with respect to any other method orcomposition described herein.

The use of the word “a” or “an” when used in conjunction with the term“comprising” in the claims and/or the specification may mean “one,” butit is also consistent with the meaning of “one or more,” “at least one,”and “one or more than one.”

The use of the term “or” in the claims is used to mean “and/or” unlessexplicitly indicated to refer to alternatives only or the alternativeare mutually exclusive, although the disclosure supports a definitionthat refers to only alternatives and “and/or.”

Throughout this application, the term “about” is used to indicate that avalue includes the standard deviation of error for the device or methodbeing employed to determine the value.

As used in this specification and claim(s), the words “comprising” (andany form of comprising, such as “comprise” and “comprises”), “having”(and any form of having, such as “have” and “has”), “including” (and anyform of including, such as “includes” and “include”) or “containing”(and any form of containing, such as “contains” and “contain”) areinclusive or open-ended and do not exclude additional, unrecitedelements or method steps.

Other objects, features and advantages of the present invention willbecome apparent from the following detailed description. It should beunderstood, however, that the detailed description and the specificexamples, while indicating specific embodiments of the invention, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description.

DESCRIPTION

Skin wounds, psoriasis, acne, burns, eczema, and smoking-induced injuryare important pathological conditions. Psoriasis is a chronic,immune-mediated, genetic skin disease affecting up to 2% of the world'spopulation ¹ . Approximately 80% of patients have mild-to-moderateplaque psoriasis while 20% have moderate-to-severe disease ² .Mild-to-moderate plaque psoriasis is typically managed with topicaltherapies, while the more severe forms of plaque psoriasis requirephototherapy, oral systemic therapies, or biological agents. Currentlyavailable oral systemic therapies include methotrexate, cyclosporine,acitretin, and apremilast, while biological therapies includeanti-TNF-α, anti-IL-12/23p40, and anti-IL-17A agents.

These conditions are frequently accompanied by inflammation, which canbe mediated by a number of inflammatory cytokines secreted byinflammatory cells such as lymphocytes, macrophages, and dendritic cellsand by a number of locally or regionally acting substances, such ashistamine, bradykinin, serotonin, the prostaglandins, thromboxanes,leukotrienes, and platelet-activating factor. Thus, while currentmethods of psoriasis treatment are effective, there exists a need in theart for improved therapeutic compositions and methods having improvedsafety and producing reduced recurrence rates. Accordingly, the presentdisclosure provides novel compositions and methods for treating dermalinflammatory conditions such as psoriasis.

By “dermal inflammatory conditions” is meant any condition in which theepidermis or underlying tissue exhibits conditions of inflammation. Suchconditions include certain skin wounds, acne, rosacea, burns, eczema,atopic dermatitis, contact dermatitis, seborrheic dermatitis, psoriasisand the like.

Other conditions that may be treated by the novel compositions disclosedherein include pruritus, prurigo nodularis, pityriasis lichenoides,neutrophilic disorders, pyoderma gangrenosum, Sweets Syndrome,granulomatous diseases, sarcoidosis, bullous disorders, papulosquamousdisorders, lichen planus, actinic keratosis, warts, pigmentationdisorders, post inflammatory hyperpigmentation, scars, dry skin,xerosis, keratosis pilaris, and skin conditions associated with aging,purpura, impaired wound healing, decubitis ulcers, and fibrotic skinconditions, fungal, viral and bacterial skin conditions, diabeticneuropathy, and the like. Also included are veterinary conditions suchas wound healing, allergic skin disorders, fungal and bacterial skindisorders, fibrotic skin conditions and the like.

To accomplish treatment of these conditions the present disclosureprovides novel systems or kits. These systems include a variety ofindividual components that when combined provide for beneficial andimproved treatment of dermal inflammatory conditions.

A first component of the system is a treatment gel. This componentcomprises active anti-inflammatory active ingredients including aturmeric extract comprising turmeric, curcumin and/or other curcuminoidsand a variety of anti-inflammatory non-curcuminoids includingdiarylheptanoids, diarylpentanoids, phenylpropenes, phenylpropenes,monoterpenes,sesquiterpenes, diterpenes, triterpenes, sterols andalkaloids. In addition, the treatment gel comprises a topical carrier.In some embodiments cyclodextrin is used in the treatment gel. In someembodiments coal tar is used in the treatment gel. In some embodimentsthe concentration in the formulation may be from 0.05% to 5.0%. In someembodiments coal tar is found in the treatment gel at a finalconcentration of around 1% w/v. In some embodiments the treatment gelcomprises curcumin, and bromelain and a topical carrier. In someembodiments salicylic acid or bromelain may be used in the treatment gelbut may alternatively or in addition be used in other components of thesystem. In some embodiments the treatment gel comprises turmeric andcurcuminoids.

Anti-TNF-α therapies have become the mainstay of systemic therapy forboth psoriasis and psoriatic arthritis. Curcuminoids, such as curcumin,demethoxycurcumin, and bisdemethoxycurcumin, and metabolites thereof arecomponents of the spice turmeric and have been recommended for a numberof medical applications ³ . Research has suggested curcuminoids cansuppress the production of TNF-α from macrophages ⁴ . It is also beenshown that activation of NF-κB can be down-modulated by curcumin ⁵ andthis down-regulation of NF-κB plays a major role in TNF-α suppression.Over 60 clinical trials have evaluated the safety and efficacy ofcurcumin in humans plus another 35 clinical trials are furtherevaluating its efficacy ⁴ . Curcumin has been found to be effective inTNF-α-associated human diseases, such as rheumatoid arthritis, Crohn'sdisease, and psoriasis. There are several reasons to believe thatcurcumin or curcuminoids may have potential for treating psoriasis,including its phototoxic effect ⁶ , its anti-psoriatic activity in themodified mouse tail test ⁷ , its inhibition of the proliferation ofhuman keratinocytes through suppression of pro-inflammatory pathways^(8, 9) , and its ability to reverse the anti-apoptotic function ofTNF-α in skin cells ¹⁰ . Furthermore, it has shown potentially promisingresults in two human studies of psoriasis ^(11, 12) . However, thepresent disclosure for the first time provides for the use of turmeric,curcumin and/or curcuminoids and or metabolites or variants thereof incombination with bromelain for topical treatment of dermal inflammatorydisorders.

Curcuminoids may be obtained from or found in a turmeric extract or maybe synthesized as is known in the art and used as a purified synthesizedproduct. In some embodiments, curcuminoids may be hydrogenated. In someembodiments the curcuminoids may be tetrahydrocurcuminoids,hexahydrocurcuminoids and octahydrocurcuminoids, or combinationsthereof. In some embodiments curcuminoid modifications includemethylation, demethylation, and/or hydrogenation or dehydrogenation andthe like.

Sources of curcuminoids are readily available. Curcumin may be added tothe composition as a purified compound having the formula of Structure 1(enol form) or 2 (keto form) or salts, or variants thereof.Alternatively, curcuminoids obtained from a turmeric extract may beadded to the compositions disclosed herein. In this embodimentcurcuminoid such as curcumin, demethoxycurcumin, and/orbisdemethoxycurcumin, and variants or metabolites thereof, and otherbioactive agents, such as, but not limited to polyphenols, terpenes andisoflavones may be included in the compositions disclosed herein. Inaddition, the treatment gel may contain butylene glycol, capryloylglycine, salicylic acid and/or citric acid. Other components may includedisodium EDTA, hydroxyethyl acrylate/sodium acryloyldimethyl tauratecopolymer, oleth-3 phosphate, PEG-7 trimethylolpropane coconut ether,polyacrylate crossploymer-6, phenoxyethanol, potassium sorbate,cyclodextrin, polyisobutene, sodium bisulfite, sodium hydroxide,tocopheryl acetate, transcutol CG, and/or undecylenoyl glycine. In someembodiments curcumin may be in a nano or nanoemulsified form asdisclosed in US20120052095, which is expressly incorporated herein byreference.

While the prior art has indicated that the use of curcuminoids at afinal concentration of greater than 0.1% is required to observe effects,the present disclosure provides for the use of curcumin at a finalconcentration of less than 0.1%. In one embodiment curcuminoids are usedat a final concentration of 0.001% to less than 0.1%. In one embodimentcurcuminoids are used at a final concentration of 0.005% to around0.075%. In one embodiment curcumin is used at final concentration of0.01 to around to around 0.05%. In one embodiment curcuminoids are usedat a final concentration of around 0.05%. In some embodimentshydrogenated curcuminoids, such as but not limited to tetrahydrocurcuminmay be used at a concentration of from 0.01 up to 2% w/v. In someembodiments the concentration is from about 0.05% up to about 1.5%. Insome embodiments the concentration is from about 0.1% up to about 1%w/v.

When turmeric extract, and/or curcuminoids such as hydrogenated curcuminis used as the source of curcuminoids, the ingredient may be at a finalconcentration of 0.1% to 10%. In one embodiment the ingredient may be ata final concentration of 0.5 to 5% or from 1% to 2%.

Another component of the treatment gel or moisturizer described hereinmay be bromelain. That is, in some embodiments bromelain is found in thetreatment gel. In alternative embodiments bromelain is found in themoisturizer. Bromelain is a crude extract from the pineapple thatcontains, among other components, various closely related proteinases,demonstrating, in vitro and in vivo, anti-edematous, anti-inflammatory,keratolytic, anti-pruritic, antithrombotic, and fibrinolytic activities.The active factors involved are biochemically characterized only inpart. While bromelain has been used in oral formulations, little isknown about is effects following topical application to the skin.However, the present disclosure provides that bromelain in combinationwith turmeric extracts containing turmeric or curcumin provides foreffective treatments of dermal inflammatory conditions, such aspsoriasis, to reduce inflammation, reduce scaling, maintain remissionsand control itch. While bromelain may be isolated from pineapple, it iscommercially available from a number of sources.

In one embodiment therefore, the anti-inflammatory compositionsdescribed herein contain bromelain at a final concentration of 0.1% to10%. w/v. In one embodiment the final concentration of bromelain is from0.25% to 2% w/v. In one embodiment the final concentration of bromelainis from 0.5% to 1% w/v.

In addition, other therapeutic ingredients that find use in thecomposition include cortisones, vitamins, green tea catechins, salicylicacid, Coal Tar, lidocaine and other painkillers or anti-inflammatorymolecules. These may optionally be found in the treatment gel,moisturizer and/or antimicrobial gel as needed. In some embodiments,salicylic acid is used in the treatment gel and is found at aconcentration of about 0.01% to about 3%, in some embodiments from about0.05% to about 1%, or in some embodiments about 0.5%, all concentrationsabove w/v. In some embodiments it has been found that salicylic acidused at these concentrations in a substantially anhydrous formulationprovides surprisingly beneficial effects. In some embodiments anhydroussalicylic acid formulation or ointment is a separate component from theothers described herein. In some embodiments salicylic acid may be usedat a concentration of about 0.025%-3% w/v or from 0.05-2% w/v or from0.075% to 1.5% w/v or from 0.1% to 1% w/v or from 0.25% to 3% w/v orfrom 0.5% to 2% w/v. Benefits of using salicylic acid include but arenot limited to removing scaling and preparing the skin for improvedpenetration of other ingredients into deeper layers of the skin. Withoutbeing bound by theory it is thought that this improves the efficacy ofthe other ingredients. In some embodiments this formulation produces alow pH after initial contact with the natural low level of moisture inthe skin to effectively remove the scaling of the psoriasis patient'sskin. The treatment may be used daily, multiple times daily, weekly,bi-weekly as needed and may be used at the same time as the otherproducts contained in the system or applied as an individual treatment.This anhydrous treatment may be applied at night while other componentsof the system are applied during the day.

By “substantially anhydrous” is meant less than about 5% aqueoussolution. Such a formulation may be achieved by methods known in theart, such as but not limited to the use of gels, petrolatum and thelike.

A second component of the system disclosed herein is an antimicrobialgel. The anti-microbial gel acts to kill bacteria, viruses and fungusthat live on the skin that can trigger inflammatory flares. Theanti-microbial gel contains benzalkonium chloride and sodium chlorite,which have a direct anti-inflammatory effect on dermal inflammatory skinconditions. The anti-microbial gel has been shown to reduce odor, reduceinflammation, reduce itching, reduce pain, reduce redness and reducepsoriasis plaques and scaling. It has also demonstrated improvements inthe symptoms of eczema, insect bites and stings. In one embodiment it isapplied as a leave-on gel. In some embodiments the benzalkonium chlorideis found in the antimicrobial gel at a final concentration of around0.01% to 5% w/v. In some embodiments the final concentration is around0.1% or around 1%. Other ingredients that find use in the antimicrobialgel include disodium EDTA, PVP, sodium bicarbonate, sodium chlorite,and/or sodium hydroxide.

A third component of the system is a moisturizer. The moisturizer maycomprise bromelain and optionally may also comprise salicylic acidand/or glycolic acid and/or lactic acid. In some embodiments salicylicacid is used at a concentration from about 0.5% to about 5%,alternatively from about 1% to about 3%, alternatively from about 1.5%to about 2% w/v. In some embodiments the concentration of salicylic isabout 0.5%, about 1%, about 1.5%, about 2%, about 2.5%, or about 3%, allw/v. In some embodiments glycolic acid or lactic acid is used at aconcentration of from about 1% to about 15%, alternatively from about 2%to about 12%, alternatively from about 3% to about 10%, alternativelyfrom about 4% to about 8%. In some embodiments, glycolic acid or lacticacid is used at a concentration of about 1%, about 2%, about 3%, about4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about11%, about 12%, about 13%, about 14%, or about 15%, all w/v. In someembodiments curcuminoids and/or hydrogenated curcuminoids may be foundin the moisturizer. In addition, the moisturizer may include ammoniumlactate or a similar emollient moisturizer. By “emollient moisturizer”is meant an agent that softens and smoothens the scales of the skin,which help reduce rough, flaky skin. In one embodiment the moisturizermay include a humectant occlusive moisturizer. By “humectantmoisturizer” is meant an agent that bonds with water molecules toincrease the water content in the skin itself. Non-limiting examples ofhumectant moisturizing agents include hyaluronic acid, glycerin,propylene glycol, urea, allantoin and glycerol. In some embodiments themoisturizer contains an occlusive agent. By “occlusive agent” is meant asubstance that provides a layer of protection that helps preventmoisture (water) loss from the skin. Non-limiting examples of occlusiveagents include lanolin, petrolatum, mineral oil, sweet almond oil, cetylalcohol, ceramides and stearyl alcohol. In some embodiments vitamins,such as Vitamin A or D may be included in the moisturizing treatment. Insome embodiments, curcuminoids may be added to the moisturizingtreatment. In some embodiments indigo may be added to the moisturizingtreatment. In some embodiments strontium or calcium salts may be addedto the moisturizing treatment. Other components of the moisturizerinclude butylene glycol, hyaluronic acid, sodium bisulfite, disodiumEDTA, transcutol, bromelain, curcumin, hydrogenated curcumin,cyclopentasiloxane, isopropyl palmitate, octyl stearate, petrolatum,tocopheryl acetate, oleth-3 phosphate, phenoxyethanol, potassiumsorbate, sodium hydroxide, citric acid, cetyl alcohol, hydroxyethylacrylate/sodium acryloyldimethyl taurate copolymer, caprylic caprictriglycerides, polyisobutene, urea, allantoin, mineral oil, paraffinwax, PEG-7 trimethylol propane coconut ether, polyacrylatecrosspolymer-6, undecylenoyl glycine and/or capryloyl glycine.

Compositions of the present disclosure also contain pharmaceuticallyacceptable carriers. Conventional pharmaceutically acceptable carriersknown in the art can include alcohols, e.g., ethyl alcohol, serumproteins, hyaluronic acid, human serum albumin, emu oil, micelles,liposomes, buffers such as phosphates, water, sterile saline or othersalts, electrolytes, glycerol, hydroxymethylcellulose, propylene glycol,polyethylene glycol, polyoxyethylenesorbitan, other surface activeagents, vegetable oils, and conventional anti-bacterial or anti-fungalagents, such as parabens, chlorobutanol, phenol, sorbic acid,thimerosal, ethoxydiglycol, hydroxyethylacrylate/sodium acryloyldimethyltaurate copolymer, butylene glycol, chelating agents, such as but notlimited to EDTA (disodium EDTA), sodium bisulfite, phenoxyethanol,capryloyl glycine, undecylenoyl glycine, oleth-3 phosphate,polyisobutene, PEG-7 trimethylolpropane coconut ether, sorbitanisostearate, sodium hydroxide and the like. Apharmaceutically-acceptable carrier within the scope of the presentinvention meets industry standards for sterility, isotonicity,stability, and non-pyrogenicity. In some embodiments the compositioncontains transcutol. In some embodiment the composition contains agelling agent. In some embodiments the composition contains transcutol.In some embodiments the composition contains aloe.

Once made, the compositions find use in treating dermal inflammatorydisorders as described herein. For instance, in a method of treatmentone would apply components of the system described herein to theaffected area of the skin as needed. In some embodiments each of thesystem components on a regular and similar basis, while in otherembodiments the frequency of application of each of the components maybe administered to the affected area of the skin independently oftreatment frequency of other system components. That is, in someembodiments each component is applied daily, twice daily, every otherday, once a week, twice a week, twice a month, three times a month,monthly, and the like. In other embodiments, each system component isindividually applied to the affected area of the skin on an independentschedule. In some embodiments, the components are applied to theaffected area of the skin and left on the skin. In some embodiments thecomponents are applied during the day or some may be applied at night.

In some embodiments different components of the system are used atdifferent times and intervals. In one embodiment each of theantimicrobial gel, treatment gel and moisturizer are applied in themorning. In one embodiment in addition to usage in the morning, the theanhydrous ointment comprising salicylic acid may be used at night forthe first 2-3 weeks. In this embodiment the anhydrous ointmentpreferably contains anhydrous salicylic acid. Without being bound bytheory, the nightly use of the anhydrous ointment is thought to boostthe efficacy of the system and speed the onset and clearing of skinscaling. The result of this regimen is rapid clearing of scaling, andeffective reduction and clearing of plaque thickness, redness, itching,pain, skin cracks associated with psoriasis. This regimen helps clearthe psoriasis and helps reduce recurrences to help keep skin clear.

In some embodiments the system also includes a micro-derma roller. As isknown in the art, micro-derma rollers comprise multiple micro needles ona roller. The roller is rolled across the skin to make multiple minutewounds. Without being bound by theory it is thought that formation ofthese small wounds stimulates the production of cellular growth factorsand collagen growth. Micro-derma rollers come with needles of differentlength. For instance, in some embodiments, the needle used on themicro-derma roller described herein is from about 0.25 to 3.00 mm inlength. For use herein, preferred length are about 0.25 mm, or about 0.5mm or about 0.75 mm or about 1 mm, or about 1.5 mm or about 2 mm. Insome embodiments the needle length is from about 0.15 mm to about 2 mm,or from about 0.2 mm to about 1 mm or from about 0.25 mm to about 0.5mm. As used herein, the micro-derma roller is rolled over the treatmentarea to improve skin penetration of ingredients and improve the healingtime of the skin lesions, e.g. psoriasis lesions. In some embodimentsthe micro-derma roller roughens the skin without penetrating the dermisto create a healing response in the skin. The micro-derma rollerimproves healing time by stimulating growth factors in the skin andstimulating collagen production. The micro-derma roller may be useddaily, every other day, bi-weekly or weekly.

This system has been shown to reduce itching and pain associated withpsoriasis plaques and it has been shown to reduce redness, plaquethickness, heal cracks in skin, control odor, rejuvenate skin, softenskin, hydrate skin, moisturize skin, clear psoriasis lesions andmaintain remission of psoriasis symptoms when used regularly. Itimproves scalp psoriasis, clearing skin flaking, reducing itching andredness. It has also been shown to reduce the itch often associated witheczema and reduce the associated inflammation and redness. Accordingly,the present disclosure also provides methods of preventing recurrence ofdermal inflammatory disorders such as psoriasis. This topicalformulation system can be used concomitantly with other prescription andnon-prescription psoriasis treatments such as, topical vitamin Dpreparations, topical steroids, topical or oral retinoids, oralimmune-modulating agents or injectable biological agents, PUVA and UVlight treatments, coal tar preparations, and the like.

The system is described above including different components indifferent configurations. In some embodiments the system includessalicylic acid ointment, a psoriasis treatment gel and a therapeuticmoisturizer as described herein. In some embodiments the system includesa micro-derma roller, treatment gel and therapeutic moisturizer. In someembodiments the system includes salicylic acid ointment, micro-dermaroller, treatment gel and therapeutic moisturizer. In some embodimentsthe system includes the antimicrobial gel, treatment gel, moisturizer,dermal roller and the anhydrous salicylic acid ointment.

While the compositions and methods of this invention have been describedin terms of preferred embodiments, it will be apparent to those of skillin the art that variations may be applied to the compositions and/ormethods and in the steps or in the sequence of steps of the methoddescribed herein without departing from the concept, spirit and scope ofthe invention. More specifically, it will be apparent that certainagents which are both chemically and physiologically related may besubstituted for the agents described herein while the same or similarresults would be achieved. All such similar substitutes andmodifications apparent to those skilled in the art are deemed to bewithin the spirit, scope and concept of the present invention.

EXAMPLES

The following examples are included to demonstrate preferred embodimentsof the invention. It should be appreciated by those of skill in the artthat the techniques disclosed in the examples which follow representtechniques discovered by the inventor to function well in the practiceof the invention, and thus can be considered to constitute preferredmodes for its practice. However, those of skill in the art should, inlight of the present disclosure, appreciate that many changes can bemade in the specific embodiments which are disclosed and still obtain alike or similar result without departing from the spirit and scope ofthe invention.

Example 1

Plaque psoriasis—Older aged male with multiple plaque locations appliedthe 3-step treatment regimen daily for 3 months. Itching was resolvedwithin minutes of the first application. The redness of the lesionsbegan improving by the second week with improvements in scaling andlesion area by week four through week 8. Lesions were virtually clear bymonth 3.

Inverse psoriasis—Middle aged male with inverse psoriasis in multipleintregenous areas applied the 3-step treatment regimen for 6 weeks.During that period, itching cleared the first day, redness beganimproving in the first week and clearing of all sites occurred by week 6

Eczema—Older aged male with eczema in the groin area applied the 3-steptreatment regimen for 2 weeks to the affected area. Rapid improvement ofitching occurred during the first hour of treatment including analitching. Inflammation and eczema symptoms resolved by the end of thefirst week of treatment. In addition, the same patient reported he wasallergic to deodorants and applied the 3-step treatment regimen to theunderarm area in an attempt to control body odor. The 3-step treatmentregimen completely controlled the subject's body odor during the firstapplication and it was well tolerated. The product was used daily withexcellent results.

Example 2

Psoriasis—Middle aged male with chronic psoriasis symptoms stoppedtopical psoriasis treatment 3 weeks prior. Psoriasis symptoms werebecoming significant. Person applied the psoriasis formulation alone andpsoriasis plaques cleared in 3 weeks and maintained clear with regularuse. Currently has been clear for over 5 months with very little steroidspot treatment or no steroid use. Person has never been virtually freeof psoriasis symptoms for this long of duration. Usually experiencingpsoriasis symptoms monthly. A formulation of curcumin and bromelain wasused. These results were achieved at a curcumin concentration of 0.05%and a bromelain concentration of less than 1%

Example 3

Chronic Pruritus—Middle aged male reported chronic itching symptoms onthe chest for several years. Applied to area of chronic itching. Itchingresolved in minutes. This was the first time the patient has been itchfree for years. Applied the formulation for a few days and itchingcleared for several weeks. A formulation of curcumin and bromelain wasused. These results were achieved at a curcumin concentration of 0.05%and a bromelain concentration of less than 1%.

Example 4

Psoriasis—Middle aged male with chronic psoriasis was treated with apsoriasis gel containing turmeric extract in a salicylic acid base or acoal tar base that was applied daily under occlusive patch for 19 days.The person's scaling was completely clear in less than one week using ananhydrous moisturizer pre-treatment containing 0.5% salicylic acid. Theperson received twice weekly applications of a 0.25 mm derma-roller overthe treatment site. The person achieved complete clearing of theirpsoriasis symptoms with improved skin texture and appearance in 19 daysunder occlusion using both turmeric containing formulations. Remarkably,at least one treatment patch site still remains clear of psoriasiscompared to surrounding untreated plaque after 6 months of ending thestudy.

Psoriasis—Middle aged male with moderate to severe plaque psoriasis wastreated with the 3-product treatment system after failing a course ofinjectable biological TNF alfa treatment and experiencing severe sideeffects. Subject demonstrated rapid clearance of scaling in one week.Itching and pain improved in the first week. Skin cracking improved over3 weeks. Plaque thickness and redness subsided during next 3 months withvirtually complete clearing in 5 months. Subject continues to remainclear of psoriasis plaques with continued treatment and now wears shortsin public for the first time in many years.

Psoriasis—Middle aged female with moderate plaque psoriasis was treatedwith the 3-product treatment system after stopping injectable biologicalIL-23 treatment when their health insurance would no longer providereimbursement coverage of the expensive biological. Subject demonstratedrapid clearance of scaling in one week and saw significant reductions inredness and plaque thickness in 2 months. Itching and pain subsided inthe first week. Subject's psoriasis plaques were healed by month threewith only minor pinkness of skin remaining. Psoriasis lesions were nolonger raised compared to nearby normal skin. The subject experiencedcontinuous improvement over 3 months and subject remains virtually clearof psoriasis plaques with continued use.

Psoriasis—Nine subjects with mild to moderate plaque psoriasisparticipated in a 6-week clinical study using the 3-system psoriasistreatment system. Subjects showed statistically significant improvementsin IGA scores at week 2 and week 6. Of the 9 subjects completing thestudy, 8 subjects (88.9%) demonstrated improvement compared to baseline.By week 6 there was a statistical improvement in scaling, dermalirritation and total symptom score. There was a numerical improvement inerythema and plaque thickness by week 6. Although there was clinicalimprovement, plaque thickness and erythema typically takes the longestto resolve. The subjects rated the products after 6 weeks of use and100% reported Products feel nice on skin, Products are not greasy,Products are easy to use, Products spread easily, Products do not have abad smell, I like the products, I would like to continue using theproducts.

REFERENCES

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1. A system for treating dermal inflammation said system comprising: a.an anti-microbial gel comprising sodium chlorite; b. a treatment gelcomprising at least one curcuminoid; and c. a moisturizer comprisingbromelain.
 2. The system according to claim 1 wherein each of saidanti-microbial gel, treatment gel and moisturizer are in separatecontainers.
 3. The system according to claim 1, wherein saidanti-microbial gel further comprises benzalkonium chloride.
 4. Thesystem according to claim 3, wherein the final concentration ofbromelain in said treatment gel is 0.1% to 10%.
 5. The system accordingto claim 1, wherein said treatment gel further comprises salicylic acid.6. The system according to claim 5, wherein said salicylic acid issubstantially anhydrous.
 7. The system according to claim 1 wherein saidcomposition comprises a pharmaceutically acceptable carrier for topicalapplication.
 8. The system according to claim 1, wherein the finalconcentration of curcuminoid in the treatment gel is from 0.001% to lessthan 2.0%.
 9. The system according to claim 1, wherein thepharmaceutically acceptable carrier comprises transcutol and a gellingagent.
 10. A method of treating dermal inflammation of a patientcomprising applying the anti-microbial gel, treatment gel andmoisturizing cream of the system according to claim 1 to the skin of apatient in need thereof, whereby dermal inflammation of said patient isreduced.
 11. A composition comprising curcumin, bromelain and apharmaceutically acceptable carrier for topical application.
 12. Thecomposition according to claim 11, wherein the final concentration ofcurcumin in the composition is from 0.001% to less than 0.1%.
 13. Thecomposition according to claim 11, wherein the final concentration ofbromelain is 0.1% to 10%.
 14. The composition according to claim 11,wherein the pharmaceutically acceptable carrier comprises transcutol anda gelling agent.
 15. The composition according to claim 11 furthercomprising salicylic acid.
 16. The composition according to claim 15,wherein said salicylic acid is at a concentration from 0.25% to 3% w/v.17. A method of treating psoriasis comprising applying a compositionaccording to claim 11 to the skin of a patient in need thereof.
 18. Akit comprising the system according to claim 1 and further comprising aderma roller.
 19. The kit according to claim 18, wherein said dermaroller comprises needles of 0.2 mm to about 1 mm in length.